Effects of scavenger receptor A and the methylation of its promoter DNA on homocysteine-induced atherosclerosis

ZHANG Jing☆; ZHANG Zi-xin; JIANG Yi-deng

doi:10.13820/j.cnki.gdyx.20183771

Abstract：Objective To investigate the effects of scavenger receptor A and the methylation of its promoter DNA on homocysteine – induced atherosclerosis. Methods ApoE-/- mice were fed with high methionine diet for 16 weeks to replicate the HHcy animal model (Meth group), while normal control group (C57BL/6J mouse fed with normal diet, N-control group ) and model control group (ApoE-/- mouse fed with normal diet, A- control group) were set up. Aortic frozen sections were made and performed with HE and oil red O staining to observe the degree of atherosclerosis in mice. The levels of serum Hcy and blood lipid were measured by automatic biochemical analyzer. THP-1 derived macrophages were treated with oxidized low- density lipoprotein to replicate the foam cell model. Oil red O staining was performed to determine the success of replication. The foam cells were treated with 0, 50, 100, 200, and 500μmol/L Hcy, and 50 μmol/L Hcy +10 μmol/L AZC, respectively. The expression of SR- A in aorta of mice and foam cells was assessed by real- time quantitative PCR (RT-qPCR). The methylation level of SR- A DNA in mouse aorta and foam cells was determined by nested methylation specific PCR (nMS- PCR). The effect of DNA methylation inhibitor (AZC) on lipid accumulation foam cells was also detected. Results Compared with control groups, the serum Hcy in Methy group was significantly higher (P＜0.01）， with significant arthrosclerosis in aorta. Compared with control groups, significant up- regulation of SR- A mRNA was observed in Methy group and Hcy stimulation foam cells (P＜0.01）; however, o significant difference in SR- ARNA methylation was observed. Conclusion The down- regulation of SR- A plays and important role in Hcy- induced arthrosclerosis. The over-expression of DNMT1 induces this process, probably via the methylation of SR- A promoter.